Accounts of Chemical Research最新文献

{"title":"","authors":"Guozhi Xiao*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 14","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":16.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Ona Ambrozaite, Reynolds Dziobek-Garrett and Thomas J. Kempa*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 14","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":16.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asymmetric Catalytic Radical Reactions Enabled by Chiral N,N'-Dioxide-Metal Complexes.","authors":"Weidi Cao,Xiaohua Liu,Xiaoming Feng","doi":"10.1021/acs.accounts.5c00370","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00370","url":null,"abstract":"ConspectusThe strategic implementation of asymmetric catalytic radical reactions has evolved into a sophisticated methodology for constructing stereogenic centers, driven by remarkable advancements in radical generation techniques. However, achieving high stereoselectivity remains a formidable challenge due to the inherent high reactivity, transient lifetime of radical species, and presence of competing racemic background pathways. Addressing these limitations necessitates precise catalytic systems capable of orchestrating radical generation and enantioselective transformation in a controlled manner. In this Account, we systematically present our recent progress in enantioselective radical transformations mediated by chiral N,N'-dioxide-metal complexes, which have previously been widely used in polar reactions. Our mechanistic investigations categorize these transformations into three distinct paradigms based on radical generation strategies. (1) Oxidant-driven radical generation: Leveraging oxidants─hypervalent iodine reagents, peroxides, or molecular oxygen─we achieved alkyl radical formation. By synergizing these oxidants with redox-active or redox-inert chiral N,N'-dioxide-metal catalysts, we accomplished asymmetric difunctionalization of both electron-deficient and electron-rich olefins, alongside enantioselective radical cross-coupling reactions. (2) Merging photocatalytic strategy: Visible light irradiation facilitates the activation of metallic or organic photocatalysts (PCs), generating excited state species for redox or hydrogen atom transfer (HAT) processes. This enables the selective cleavage of inert C(sp3)-H bonds in hydrocarbons or C(sp2)-H bonds in aldehydes, producing diverse radical intermediates. Integration with chiral Lewis acid catalysts allows enantioselective radical additions to ketones, imines, and α,β-unsaturated carbonyl compounds, establishing C-C bonds under mild conditions without use of preactivated radical generators. Furthermore, energy-transfer photocatalysis combined with chiral Lewis acids promotes cyclization via C═C bond activation. Besides, an electron-shuttle strategy has been developed to balance radical generation from photoactive substrates, enabling asymmetric acylation and alkylation of aldimines. (3) Lewis acid-enabled substrate photoexcitation: We disclosed photocatalyst-free approaches wherein chiral N,N'-dioxide-metal complexes modulate substrate photophysics. Chiral Lewis acid coordination with several carbonyls or imines alters their photochemical properties. Interestingly, this activation of some C═X unsaturated compounds under light enhances their reduction potentials for single electron transfer (SET) as a temporary oxidant, enabling direct radical alkylation of ketones/imines. Alternatively, the strategy can stabilize triplet excited states.Collectively, our studies elucidate mechanistic frameworks for stereocontrol in radical reactions, demonstrating the versatility of chiral Lewis acid cat","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"29 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When gem-Diborylalkanes Meet Carboxylic Acids and Their Derivatives: Enolate/Enamine Chemistry beyond Conventional Reactivity.","authors":"Tongchang Fang,Bowen Ren,Chao Liu","doi":"10.1021/acs.accounts.5c00373","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00373","url":null,"abstract":"ConspectusThe booming progress of organoboron chemistry has unleashed a profound revolution in the field of synthetic chemistry. Among emerging organoboron reagents, gem-diborylalkanes stand out as uniquely versatile platforms that unlock unconventional reaction pathways through activation of their dual boryl groups. The empty p orbitals of adjacent the boryl groups not only allow generation of α-boryl carbanionic intermediates but also enable precise selectivity controls, allowing chemists to navigate a previously inaccessible chemical space.In this Account, we summarize our systematic exploration of gem-diborylalkanes as multiple nucleophiles in reactions with carboxylic acid derivatives as multiple electrophiles, revealing boron enolate/enamine intermediates as linchpins for efficient functional group interconversions.Our journey began with a breakthrough in the direct deoxygenative enolization of carboxylic acids using gem-diborylalkanes. In that work, carboxylic acids participated in the enolization reaction as an acyl source for the first time. Electrophilic capture of the resulting boron enolates enables dual functionalization of gem-diborylalkanes to yield various α-functionalized ketones. Expanding this paradigm to amide systems, we discovered that amide activation follows distinct mechanistic divergences. While tertiary amides undergo B-N elimination to generate enol species, primary/secondary amides and lactams preferentially undergo B-O elimination to form enamine intermediates. This result provides a strategic blueprint for synthesizing α-functionalized ketones, enamides, and cyclic amines from common amides through substrate-controlled chemoselectivity. Revisiting the reaction of lithiated gem-diborylalkanes with carboxylic esters, we developed an enolate-O trapping strategy that revolutionized alkyne synthesis. Reaction of lithiated gem-diborylalkanes with esters generates α-boryl boron enolates, which upon α,β-[B-O] elimination with a novel trapping reagent produce alkynes with high efficiency. The versatility of this method extends to the precision synthesis of 13C-labeled alkynes using isotopically labeled gem-diborylmethane. Pursuing the chemistry of lithiated gem-diborylalkanes with nitriles, we achieved a remarkable atom swap in the triple bond through α-boryl enamine intermediates. The reaction cascade between lithiated gem-diborylalkanes and nitriles, mediated by tert-butyl nitrite (TBN) as a N-deleting reagent, accomplishes an efficient swap of N-to-C bonds within triple bonds. This \"atom transposition\" strategy expands the synthetic toolbox for accessing functionalized alkynes from readily available nitriles.Through these case studies, we demonstrate how a systematic investigation of boron effects can rewrite textbook synthesis. The developed methodologies not only solve long-standing synthetic challenges in functional group interconversion but also establish gem-diboryl chemistry as a conceptual framework for designing n","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"1 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Competition between Nucleic Acids and Intrinsically Disordered Regions within Proteins.","authors":"Xi Wang,Yaakov Levy,Junji Iwahara","doi":"10.1021/acs.accounts.5c00261","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00261","url":null,"abstract":"ConspectusIntrinsically disordered regions (IDRs) are important components of protein functionality, with their charge distribution serving as a key factor in determining their roles. Notably, many proteins possess IDRs that are highly negatively charged, characterized by sequences that are rich in aspartate (D) or glutamate (E) residues. Bioinformatic analyses indicate that negatively charged, low-complexity IDRs are significantly more common than their positively charged counterparts rich in arginine (R) or lysine (K). For instance, sequences of 10 or more consecutive negatively charged residues (D or E) are present in 268 human proteins. In contrast, the corresponding sequences of 10 or more consecutive positively charged residues (K or R) are present in only 12 human proteins. Interestingly, about 50% of proteins containing D/E tracts function as DNA-binding or RNA-binding proteins. Negatively charged IDRs can electrostatically mimic nucleic acids and dynamically compete with them for DNA-binding domains (DBDs) or RNA-binding domains (RBDs) that are positively charged. This leads to a phenomenon known as autoinhibition, in which the negatively charged IDRs inhibit binding to nucleic acids by occupying the binding interfaces within the proteins through intramolecular interactions.Rather than merely reducing binding activity, negatively charged IDRs offer significant advantages for the function of DNA/RNA-binding proteins. The dynamic competition between negatively charged IDRs and nucleic acids can accelerate the target search processes for these proteins. When a protein encounters DNA or RNA, the electrostatic repulsion force between the nucleic acids and the negatively charged IDRs can trigger conformational changes that allow the nucleic acids to access DBDs or RBDs. Additionally, when proteins are trapped at high-affinity nontarget sites on DNA or RNA (\"decoys\"), the electrostatic repulsion from the negatively charged IDRs can rescue the proteins from these traps. Negatively charged IDRs act as gatekeepers, rejecting nonspecific ligands while allowing the target to access the molecular interfaces of DBDs or RBDs, which increases binding specificity. These IDRs can also promote proper protein folding, facilitate chromatin remodeling by displacing other proteins bound to DNA, and influence phase separation, affecting local pH. The functions of negatively charged IDRs can be regulated through protein-protein interactions, post-translational modifications, and proteolytic processing. These characteristics can be harnessed as tools for protein engineering. Some frame-shift mutations that convert negatively charged IDRs into positively charged ones are linked to human diseases. Therefore, it is crucial to understand the physicochemical properties and functional roles of negatively charged IDRs that compete with nucleic acids.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"11 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Mass Growth Processes to Polycyclic Aromatic Hydrocarbons through Radical-Radical Reactions Exploiting Photoionization Reflectron Time-of-Flight Mass Spectrometry.","authors":"Shane J Goettl, Musahid Ahmed, Alexander M Mebel, Ralf I Kaiser","doi":"10.1021/acs.accounts.5c00311","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00311","url":null,"abstract":"<p><p>ConspectusPolycyclic aromatic hydrocarbons (PAHs) represent critical building blocks in molecular mass growth processes to carbonaceous nanoparticles, referred to as interstellar and circumstellar grains along with soot particles in astrophysical environments and combustion systems, respectively. Recent advancements on elucidating elementary steps to PAHs have utilized reactions of aromatic radicals, resonantly stabilized free radicals, and aliphatic radicals with closed shell hydrocarbons. However, the role of radical-radical reactions (RRRs) leading to PAHs has remained largely unexplored on the molecular level due to preceding experimental challenges in producing sufficiently high number densities of radical reactants for isomer-selective detection of products from bimolecular and termolecular reactions. This Account offers the latest developments in our knowledge on the mechanisms and pathways to PAHs via RRRs probed in a chemical microreactor at temperatures as high as 1600 K. Product preservation in a molecular beam coupled with synchrotron vacuum ultraviolet photoionization reflectron time-of-flight mass spectrometry and photoelectron photoion coincidence spectroscopy enabled isomer-selective detection of PAHs of up to three rings by their photoionization efficiency curves, which were fit with a linear combination of reference curves for identification. Experiments were combined with computational fluid dynamics modeling of the physicochemical processes in the microreactor, as well as high-level electronic structure calculations to reveal the reaction pathways of each system. Six distinct reaction mechanisms were discovered in this work: propargyl addition─benzannulation (PABA), methyl addition─ring expansion (MARE), cyclopentadienyl addition─naphthylization (CPAN), fulvenallenyl addition─cyclization─aromatization (FACA), benzyl addition─aromatization (BAA), and phenyl addition─pentacyclization (PAP). By systematically varying the number of carbon atoms in the radical reactants, molecular mass growth processes involving reactions between radicals with odd numbers of carbon atoms access aromatics carrying one, two, or three six-membered rings, whereas reactions between even- and odd-carbon-numbered radicals produce aromatics combining five- and six-membered rings. Our investigations reveal unconventional cycloadditions on excited state triplet surfaces, additions of radicals to low spin density carbon-centered radicals, spiroaromatic and fulvene-type intermediates, and highly strained bicyclic reaction intermediates, challenging current perceptions of PAH molecular mass growth processes. All of the listed mechanisms, except for FACA, feature endoergic reactions or barriers which lie above the separated reactants and therefore might be central to circumstellar environments of carbon-rich stars and planetary nebulae as their descendants, but they play no role in the gas phase of cold molecular clouds where temperatures as low as 10 K do","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fundamental Insights for Practical Electrocatalytic CO2 Reduction.","authors":"Wensheng Fang,Mingzhi Wang,Lebin Cai,Bao Yu Xia","doi":"10.1021/acs.accounts.5c00154","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00154","url":null,"abstract":"ConspectusGlobal energy's continuous reliance on fossil fuels has driven unprecedented CO2 emission growth, intensifying climate volatility through heightened frequency and severity of extreme weather events. These crises underscore the critical need for accelerating innovation in sustainable energy technologies capable of reconciling two urgent imperatives: ensuring reliable energy access while delivering measurable progress toward global decarbonization commitments. Electrocatalytic CO2 reduction reaction (CO2RR) technology implementation could not only help to reduce CO2 concentrations in the atmosphere but also provide new possibilities for renewable energy storage, thus playing a crucial role in driving the energy transition and achieving carbon neutrality. To advance the industrialization of this technology, multiple global companies (Sunfire, Germany; Dioxide Materials, USA; Carbon Energy Technology, China, etc.) have initiated pilot-scale research. However, progress has been slow due to challenges related to catalyst, electrode, and electrolyzer design. Through integrated optimizations spanning catalyst structural engineering, electrode configuration fabrication, and electrolyzer system design, we have demonstrated progressive milestones in the technology of CO2RR.This Account systematically presents our research group's groundbreaking contributions to practical CO2RR, spanning catalyst design, electrode architecture fabrication, and advanced electrolyzer development. Based on the current research foundation in our group, we contend that for the industrial-scale development of CO2 reduction reactions, greater emphasis should be placed on catalyst stability rather than solely on catalytic activity. To improve the stability of catalytic systems, several strategies can be implemented, including enhancing electron transfer rate and strengthening interatomic bonds to mitigate catalyst degradation during operation. We have also proposed a strategy for customizing highly efficient catalysts by simulating the degradation path of the catalyst. In addition, we also advocate heightened attention to electrode fabrication processes, encompassing structural design and paired electrolysis configurations, as these factors critically influence the overall system's conversion efficiency, stability and ultimately the economic viability of industrial applications. Additionally, we highlight our progress in electrolyzer research, particularly demonstrating the advantages and potential of the proton exchange membrane (PEM) electrolyzer in CO2 reduction systems. Given their ability to concurrently address challenges such as high CO2 loss rates and the carbonate deposition problem, we propose that this direction needs superior development to advance CO2RR industrialization. Finally, we summarize this Account and propose future research directions, focusing on scalable production of catalysts, CO2 capture technologies, direct flue gas electrolysis, system integra","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"67 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycome-Proteome Interactome Cartography via Proximity Tagging.","authors":"Patrick Tseng,Mia L Huang","doi":"10.1021/acs.accounts.5c00314","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00314","url":null,"abstract":"ConspectusGlycans are now recognized as essential biomolecules for life, and an increasing number of investigators and studies continue to reveal the myriad ways in which these post-translational modifications regulate important biological events. Chief among the ways in which glycans carry out their roles is by engaging in binding interactions with glycan-binding proteins (GBPs). Such interactions are important for proper physiology or in the activation of disease. Thus, achieving a precise molecular understanding of these interactions can pave new avenues for synthetic control and potentially therapeutic strategies to regulate disease. In this Account, we discuss our efforts toward revealing the collective interactions between glycans, protein glycoconjugates, and GBPs in cells, with an eye toward identifying the specific glycan-carrying proteins that interact with the GBPs in a functional manner.While the importance of studying glycan-GBP interactions has long been established, prior to our work, much of glycoscience had been occupied with the systematic assignment of the structural features of glycans required for recognition by GBPs in vitro, often using homogeneous glycan arrays. This important body of work enabled the preliminary identification of principal GBP-glycan binding preferences and allowed the rational design of functionalized glycan molecules to use as competitive inhibitors. Equipped with these two sets of important tools, expanding our understanding of glycan-GBP interactions from in vitro glycan binding preferences toward that of glycoprotein-GBP interactions in vivo has become timely and possible. We describe the conceptual motivation behind developing proximity tagging technologies to capture these glycoprotein-GBP interactions and how we used these interactome data sets to guide the discovery of functional interactors or create new hypotheses. Furthermore, we describe how proximity tagging can continuously be used toward application in our work, and the potential routes of investigation it may facilitate in the coming years.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"38 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144566691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct Reductive Transformation of Amides: From Methodology Development to Applications in Total Synthesis.","authors":"Wei Ou,Pei-Qiang Huang","doi":"10.1021/acs.accounts.5c00366","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00366","url":null,"abstract":"ConspectusEfficiency, selectivity, versatility, and practicality are major goals in current organic synthesis. Carboxamides are among the most prevalent and versatile functional groups in organic and medicinal chemistry, prominently featured in pharmaceuticals, natural products, and biomolecules. A large-scale analysis of over 1 million pharmaceutical reactions revealed that amide formation is the most frequently used transformation, and amine synthesis remains a foundational transformation in medicinal chemistry. Among various approaches, the reductive functionalization of amides has emerged as a particularly powerful strategy, especially in the concise synthesis of nitrogen-containing alkaloids with diverse biological activities.However, the exceptional stability of amides, due to resonance delocalization, renders them chemically inert toward nucleophilic addition and thus difficult to transform directly. Traditional strategies often require multistep protocols or harsh reagents, thereby limiting their efficiency, selectivity, and compatibility with sensitive functional groups.Our group has contributed significantly to overcoming these challenges by developing general and chemoselective methods for the direct reductive transformation of amides. Since our initial reports in 2010, we have introduced multiple mechanistic paradigms─including triflic anhydride activation and fully catalytic relay processes─that enable the efficient synthesis of α-functionalized amines and alkaloids. These include direct reductive alkylation, bisalkylation, and more recently, catalytic enantioselective reductive alkynylation and alkylation of both secondary and tertiary amides.In this Account, we summarize over a decade of progress in this area, focusing on the development of new activation strategies (e.g., Ir-Cu relay catalysis, organocatalyst integration, Pd-mediated tandem transformations), mechanistic understanding, and synthetic applications. We highlight how our catalytic asymmetric methodologies have redefined the utility of amides as building blocks, enabling highly efficient and selective construction of complex nitrogen heterocycles and natural products. Moreover, we discuss the broader implications of these advances in medicinal chemistry and process-scale synthesis. The impact of these methodologies is further demonstrated through their adoption by other research groups in total synthesis and drug development, underscoring their generality and transformative potential.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"24 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycosyl ortho-(1-Phenylvinyl)benzoates as Donors for Streamlined One-Pot Assembly of Carbohydrates from Oligosaccharides to Polysaccharides.","authors":"Guozhi Xiao","doi":"10.1021/acs.accounts.5c00387","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00387","url":null,"abstract":"ConspectusCarbohydrates are essential and the most abundant biomolecules, with pivotal roles in numerous biological processes. However, in comparison with proteins and DNA, the biosynthesis of carbohydrates is not a template-driven process but instead a stepwise process, which results in heterogeneous and complex carbohydrate structures. The accessibility of well-defined, pure, and sufficient glycans remains a bottleneck in carbohydrate chemistry, impeding the in-depth biological and functional studies and development of carbohydrate-based therapeutics. To address this issue, we have developed new glycosylation reactions with glycosyl ortho-(1-phenylvinyl)benzoates (PVBs) as versatile donors and new one-pot glycan assembly strategies on the basis of PVB glycosylation for the streamlined synthesis of carbohydrates from oligosaccharides to polysaccharides.The advantages of this new glycosylation reaction protocol include the following: (1) glycosyl PVB donors are readily prepared and shelf-stable, (2) promoters such as NIS and TMSOTf are cheap and readily available, (3) glycosylation yields are generally good to excellent with few side reactions, (4) substrate scopes are broad, (5) the operation of the method is simple, and (6) the method is suitable for the one-pot assembly of glycans. Different from traditional carbohydrate synthesis that is stepwise, tedious, and time-consuming, new one-pot glycan assembly strategies based on PVB donors not only accelerated the synthesis and reduced chemical wastes but also precluded potential issues such as aglycone transfer, undesired interferences of the departing species, and unpleasant odor inherent to one-pot glycosylation with thioglycosides. These one-pot glycan assembly strategies mainly include four tactics: (1) by utilizing the orthogonality of PVB donors, orthogonal one-pot glycosylation could construct diverse glycosidic bonds, including the challenging 1,2-cis-glycosidic linkages, through strategic combinations of PVB donors with the other donors such as glycosyl trichloroacetimidate, N-phenyltrifluoroacetimidate, and ortho-alkynylbenzoates; (2) by utilizing the high reactivity of PVB donors, reactivity-based one-pot glycosylation could achieve efficient glycan assembly via the combinations of PVB donors with thioglycosides or n-Pen glycosides; (3) through preactivation of PVB donors, preactivation-based one-pot glycosylation could achieve the efficient assembly of different glycosidic linkages, especially 1,2-cis-glycosidic bonds; and (4) through utilizing the orthogonality and reactivity of PVB donors, orthogonal and reactivity-based one-pot glycosylation could construct at least four different glycosidic bonds simultaneously. Indeed, one-pot glycan assembly strategies on the basis of PVB glycosylation method have been successfully applied to the streamlined total synthesis of diverse and complex carbohydrates with important biological activities, including plants glycans such as the undecasaccha","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"70 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}